Missense variant in the protease-like domain of apolipoprotein(a) causing markedly elevated Lp(a) levels and substantially increased risk of coronary artery disease, peripheral vascular disease, and aortic valve stenosis; carriers show differential benefit from aspirin therapy

Phase I detoxification enzyme that hydroxylates estradiol to potentially genotoxic 4-hydroxyestradiol and activates environmental procarcinogens including PAHs

Intronic TCF7L2 variant tagging the diabetes-risk haplotype and associated with elevated proinsulin/insulin ratio through impaired beta-cell insulin processing

Intronic variant in clusterin gene affecting Alzheimer's disease risk through regulation of amyloid-beta clearance

Intronic variant in ADH5 (GSNOR) in near-complete LD (r²=0.99) with adjacent promoter SNPs at a potential NF-κB binding site; the common A allele tags the asthma risk haplotype associated with elevated GSNOR transcription, GSNO depletion, and increased childhood asthma susceptibility, while the protective T allele is associated with reduced GSNOR expression and lower asthma risk

TGF-beta signaling regulator variant identified as the top shared locus between migraine and type 2 diabetes

Nucleotide diphosphatase that inactivates toxic thiopurine metabolites; reduced function causes severe myelosuppression at standard drug doses

Rare AMPK beta-1 subunit variant linking central energy sensing to shared migraine and type 2 diabetes susceptibility

Modulates local cortisol activation from cortisone in liver and adipose tissue, influencing visceral fat, insulin sensitivity, and metabolic syndrome risk

Nonsense variant creating a premature stop codon at amino acid 2279 of apolipoprotein B-100, producing a severely truncated apoB-50 protein and causing familial hypobetalipoproteinemia type 1 with markedly reduced LDL cholesterol and hepatic steatosis risk